2019
Integrin α5β1 regulates PP2A complex assembly through PDE4D in atherosclerosis
Yun S, Hu R, Schwaemmle ME, Scherer AN, Zhuang Z, Koleske AJ, Pallas DC, Schwartz MA. Integrin α5β1 regulates PP2A complex assembly through PDE4D in atherosclerosis. Journal Of Clinical Investigation 2019, 129: 4863-4874. PMID: 31408443, PMCID: PMC6819111, DOI: 10.1172/jci127692.Peer-Reviewed Original ResearchConceptsPP2A regulatory subunit B55αTranscription factor YAPActive PDEComplex assemblyAdapter rolePDE4D5B55αIntegrin α5EC phenotypeCell functionInflammatory signalingAthero-prone regionsActivationComplexesPP2AInflammatory activationWidespread consequencesDephosphorylationProteomicsVascular remodelingPlaque sizeAtherosclerotic plaque sizeSignalingYAPRegulates
2016
Interaction between integrin α5 and PDE4D regulates endothelial inflammatory signalling
Yun S, Budatha M, Dahlman JE, Coon BG, Cameron RT, Langer R, Anderson DG, Baillie G, Schwartz MA. Interaction between integrin α5 and PDE4D regulates endothelial inflammatory signalling. Nature Cell Biology 2016, 18: 1043-1053. PMID: 27595237, PMCID: PMC5301150, DOI: 10.1038/ncb3405.Peer-Reviewed Original ResearchConceptsInflammatory signalingIntegrin α5Enhanced phosphodiesterase activityExtracellular matrix remodellingModulates inflammationTherapeutic targetInflammationProstacyclin secretionLipid metabolismEndothelial cellsMatrix remodellingVivo knockdownECM remodellingBasement membraneIntegrin α2Phosphodiesterase activityMolecular mechanismsRemodellingΑ5Direct bindingSignalingCellsFibronectinAtherosclerosisArtery
2010
Atheroprone Hemodynamics Regulate Fibronectin Deposition to Create Positive Feedback That Sustains Endothelial Inflammation
Feaver RE, Gelfand BD, Wang C, Schwartz MA, Blackman BR. Atheroprone Hemodynamics Regulate Fibronectin Deposition to Create Positive Feedback That Sustains Endothelial Inflammation. Circulation Research 2010, 106: 1703-1711. PMID: 20378855, PMCID: PMC2891748, DOI: 10.1161/circresaha.109.216283.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortic DiseasesApolipoproteins EAtherosclerosisCells, CulturedDisease Models, AnimalEndothelium, VascularFeedback, PhysiologicalFibronectinsHemodynamicsHumansInflammationMechanotransduction, CellularMiceMice, Inbred C57BLMice, KnockoutNF-kappa BPlatelet Endothelial Cell Adhesion Molecule-1Pulsatile FlowRegional Blood FlowRNA InterferenceStress, MechanicalTime FactorsTransfectionUp-RegulationConceptsFN depositionAtheroprone flowPECAM-1FN expressionTranscription factor NF-kappaB.Platelet endothelial cell adhesion moleculeNF-kappaB activationNF-kappaB activityAtheroprone hemodynamicsHuman endothelial cellsEndothelial inflammationProinflammatory phenotypeAortic archInduction of fibronectinCarotid arteryCell adhesion moleculeExogenous fibronectinInflammatory signalingFN accumulationNF-kappaBSustained increaseNF-kappaB.Nuclear factorTransient increaseEndothelial cellsMatrix-Specific Protein Kinase A Signaling Regulates p21-Activated Kinase Activation by Flow in Endothelial Cells
Funk SD, Yurdagul A, Green JM, Jhaveri KA, Schwartz MA, Orr AW. Matrix-Specific Protein Kinase A Signaling Regulates p21-Activated Kinase Activation by Flow in Endothelial Cells. Circulation Research 2010, 106: 1394-1403. PMID: 20224042, PMCID: PMC2862370, DOI: 10.1161/circresaha.109.210286.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsBasement MembraneCattleCdc42 GTP-Binding ProteinCells, CulturedCyclic AMP-Dependent Protein KinasesEndothelial CellsEnzyme ActivationEnzyme ActivatorsHumansIloprostInflammationInflammation MediatorsInjections, IntraperitonealIntegrinsMaleMechanotransduction, CellularMiceMice, Inbred C57BLNF-kappa BP21-Activated KinasesPhosphorylationProtein Kinase InhibitorsPulsatile FlowRac GTP-Binding ProteinsRegional Blood FlowStress, MechanicalTime FactorsTransfectionConceptsInflammatory gene expressionNF-kappaB activationInflammatory signalingEndothelial cellsProstacyclin analogue iloprostBasement membrane proteinsBlood flow patternsPKA-dependent inhibitionInflammatory pathwaysAnalogue iloprostGene expressionKappaB activationNF-kappaB.Subendothelial extracellular matrixNuclear factorPAK activationBasement membrane